engleski

Cellular Model of Parkinson`s Disease for Safety Testing of Selenium-Based Nanodelivery System

The current “gold standard” therapy is levodopa (L-DOPA) due to its effectiveness and ability to permeate the blood-brain barrier (BBB). However, long-term treatment with L-DOPA can lead to serious side effects and increase oxidative stress, thereby worsening the disease [2]. The oxidative stress caused by either L-dopa or dopamine could be lessened by the combination of antioxidants – one that promises is selenium (Se) – an essential trace element that can protect from oxidative damage through selenoproteins [3]. Direct use of Se as an antioxidant supplement is toxic due to a narrow therapeutic index, so Se should be applied in other therapeutical forms. The use of Se in the form of nanoparticles (SeNPs) may elicit the same beneficial effects with reduced toxicity [4]. This study tested the safety of SeNPs as L-DOPA carrier using differentiated neuroblastoma (SH- SY5Y) cells as in vitro model of Parkinson`s disease [5]. SeNPs were prepared via reduction of sodium selenite by L-ascorbic acid and functionalization by polysorbate 20 (SeTWEEN) and poly(vinylpyrrolidone) (SePVP). The shape, size, and surface charge of SeNPs were determined with transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential measurements, respectively. Cell viability and apoptosis induction test were performed using flow cytometry, while oxidative stress was determined by measuring the concentration od reactive oxygen species, glutathione (GSH) and mitochondrial membrane potential. In all experiments L-DOPA loaded SeNPs were compared with SeNPs and L-DOPA alone. L- DOPA loaded SeNPs (1ppm) were non-toxic to differentiated SH-SY5Y cells after 24-hour treatment, while L-DOPA reduced cell viability at the 100 μM, but not at 50 μM concentration. L-DOPA induced oxidative stress at the concentration of 100 µM which was effectively reduced after combining with SeNPs (1 ppm). Results suggest that SeNPs could be a promising approach for the reduction of toxicity caused by L-DOPA.

Parkinson`s, nano, drug-delivery

nije evidentirano